In open surgery, an experienced surgeon who has just removed a cancerous prostate can often tell by feel whether there is a safe margin of tissue covering the cancer. Tissue that seems adherent or sticky can be a red flag; so can tissue that feels hard. But in the laparoscopic and robotic forms of prostatectomy, with current techniques the prostate is usually not examined until after the operation. If only there were some way to tell in real time, during surgery, whether any cancer cells have been left behind. Soon, there may be.
Urologist Ron Rodriguez, M.D., Ph.D., The Irene and Bernard L. Schwartz Scholar, and radiologist Martin Pomper, M.D., Ph.D., The William R. Brody Professor of Radiology, and Prostate Cancer Team Scholar, believe the secret to spotting stray cancer cells may lie in an enzyme called PSMA (prostate-specific membrane antigen), which is found on the surface of prostate cancer cells. "All prostate cells make PSMA," explains Rodriguez, "but benign cells don’t make very much of it, and what they do make stays predominantly inside the cell. Prostate cancer cells, on the other hand, express PSMA right on the surface, and aggressive prostate cancer cells make even higher amounts of it. This makes it an ideal agent for targeting prostate cancer."
Using a molecule that sticks to PSMA, which they have modified to include a near-infrared fluorescent tag, Rodriguez and Pomper hope to "light up" prostate cancer cells left behind at the edges of the removed tumor during surgery, in time for the surgeon to remove them. "We have specially designed laser light sources and nearinfrared detecting cameras," says Pomper, who designed the cancer-targeting molecule, called YC-27. Before YC-27 can be tested in humans, Rodriguez and Pomper will be leading studies to make sure that the agent is safe and welltolerated, to determine how much YC-27 is needed to detect the cancer, and to refine the light source and detection equipment.
"Significant progress in imaging."
In other projects, as well, Pomper’s group has made "significant progress in imaging, and eventually therapy, of prostate cancer," Pomper reports. "First, with support originally provided by the Walsh Fund, we have developed the first 18F-labeled imaging agent for positron emission tomography (PET scanning) of PSMA, which will make prostate tumors easier to detect." Currently, notes Pomper, PET scanning is not used as much as it could be as a means of detecting prostate cancer, or of staging cancer when it is diagnosed. But in a recent small clinical trial, this new PSMA-targeting agent has proven able to show cancers that have not tomography (CT scans). "A second-generation agent has shown even higher specificity in preclinical models of prostate cancer," Pomper continues, "and it will also soon enter the clinic."
Another project in Pomper’s lab uses a clinically approved nanoparticle that finds cancer cells after they have left the prostate. Doctors have long sought a means of telling where cancer has spread, and the potential – of not only finding small bits of cancer in the body, but of treating them with the same cell-targeting technology – is vast. "This is an extension of work we published involving other cancers last year in Nature Medicine," says Pomper, "and represents the basis of a major project to be submitted for renewal of the Johns Hopkins Specialized Program of Research Excellence (SPORE) in prostate cancer research."